The role of JNK signaling in the development of nonalcoholic steatohepatitis

• Project/Area Number: 22590728
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: KODAMA Yuzo 京都大学, 医学研究科, 助教 (80378687)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: NASH / 肝線維化 / JNK / 肝細胞癌

Research Abstract

Nonalcoholic steatohepatitis (NASH) is an important pathological condition responsible for liver fibrosis and cancer. In the current study, using NASH mouse model, we analyzed the role of JNK signaling in the development of NASH and subsequent formation of liver fibrosis and cancer. As a result, the development of liver fibrosis and cancer was reduced in jnk1knockout mice as compared to wild-type mice. Furthermore, analysis of chimeric mice generated by bone marrow transplantation or in vitro experiments using primary culture cells revealed the critical role of JNK1 in non-hematopoietic cells in the development of NASH.

Research Products

• [Journal Article] Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist (2012)
  • Author(s): Iwaisako K, Haimerl M, Paik YH, Taura K, Kodama Y, Sirlin C, Yu E, Yu RT, Downes M, Evans RM, Brenner DA, Schnabl B
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 Issue: 21 Pages: 1369-76
  • DOI: 10.1073/pnas.1202464109
  • Peer Reviewed
• [Journal Article] Non-alcoholic steatohepatitis-induced fibrosis: Toll-like receptors, reactive oxygen species and Jun N-terminal kinase (2011)
  • Author(s): Brenner DA, Seki E, Taura K, Kisseleva T, Deminicis S, Iwaisako K, Inokuchi S, Schnabl B, Oesterreicher CH, Paik YH, Miura K, Kodama Y
  • Journal Title: Hepatol Res Volume: 41 Pages: 683-6
  • Peer Reviewed
• [Journal Article] Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression. (2011)
  • Author(s): Osawa Y, Seki E, Kodama Y, Suetsugu A, Miura K, Adachi M, Ito H, Shiratori Y, Banno Y, Olefsky JM, Nagaki M, Moriwaki H, Brenner DA, Seishima M
  • Journal Title: FASEB J Volume: 25 Issue: 4 Pages: 1133-44
  • DOI: 10.1096/fj.10-168351
  • Peer Reviewed
• [Journal Article] Non-alcoholic steatohepatitis-induced fibrosis : Toll-like receptors, reactive oxygen species and Jun N-terminal kinase (2011)
  • Author(s): Brenner DA, Seki E, Taura K, Kisseleva T, Deminicis S, Iwaisako K, Inokuchi S, Schnabl B, Oesterreicher CH, Paik YH, Miura K, Kodama Y
  • Journal Title: Hepatology Research Volume: 41 Issue: 7 Pages: 683-686
  • DOI: 10.1111/j.1872-034x.2011.00814.x
  • Peer Reviewed
• [Journal Article] Role and cellular source of nicotinamide adenine dinucleotide phosphate oxidase in hepatic fibrosis (2010)
  • Author(s): De Minicis S, Seki E, Paik YH, Osterreicher CH, Kodama Y, Kluwe J, Torozzi L, Miyai K, Benedetti A, Schwabe RF, Brenner DA
  • Journal Title: Hepatology Volume: 52 Issue: 4 Pages: 1420-30
  • DOI: 10.1002/hep.23804
  • Peer Reviewed
• [Journal Article] Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice (2010)
  • Author(s): Miura K, Kodama Y, Inokuchi S, Schnabl B, Aoyama T, Ohnishi H, Olefsky JM, Brenner DA, Seki E
  • Journal Title: Gastroenterology Volume: 139 Issue: 1 Pages: 323-34
  • DOI: 10.1053/j.gastro.2010.03.052
  • Peer Reviewed
• [Journal Article] Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis (2010)
  • Author(s): Inokuchi S, Aoyama T, Miura K, Osterreicher CH, Kodama Y, Miyai K, Akira S, Brenner DA, Seki E
  • Journal Title: Proc Natl Acad Sci U S A Volume: 107 Issue: 2 Pages: 844-9
  • DOI: 10.1073/pnas.0909781107
  • Peer Reviewed
• [Journal Article] Toll-like Receptor 9 Promotes Steatohepatitis via Induction of Interleukin-1beta in Mice. (2010)
  • Author(s): Miura K, Kodama Y, Inokuchi S, Schnabl B, Aoyama T, Ohnishi H, Olefsky JM, Brenner DA
  • Journal Title: Gastroenterology Volume: 139 Pages: 323-334
  • Peer Reviewed
• [Journal Article] Disruption of TAK1 in Hepatocytes Causes Hepatic Injury, Inflammation, Fibrosis and Carcinogenesis. (2010)
  • Author(s): Inokuchi S, Aoyama T, Miura K, Osterreicher CH, Kodama Y, Miyai K, Akira s, Brenner DA, Seki E.
  • Journal Title: Proc Natl Acad Sci USA. Volume: 107 Pages: 844-849
  • Peer Reviewed